Kuvarina Anastasia E, Gavryushina Irina A, Kulko Alexander B, Ivanov Igor A, Rogozhin Eugene A, Georgieva Marina L, Sadykova Vera S
Laboratory for Taxonomic Study and Collection of Cultures of Microorganisms, Gause Institute of New Antibiotics, st. Bolshaya Pirogovskaya, 11, 119021 Moscow, Russia.
Clinical Antituberculosis Center, Moscow Government Health Department Scientific, st. Stromynka, 10, 107014 Moscow, Russia.
J Fungi (Basel). 2021 Feb 21;7(2):153. doi: 10.3390/jof7020153.
Novel antimicrobial peptides with antifungal and cytotoxic activity were derived from the alkalophilic fungus VKPM F1428. We previously reported that this strain produced emericellipsin A (EmiA), which has strong antifungal and cytotoxic properties. Further analyses of the metabolites obtained under a special alkaline medium resulted in the isolation of four new homologous (Emi B-E). In this work, we report the complete primary structure and detailed biological activity for the newly synthesized nonribosomal antimicrobial peptides called emericellipsins B-E. The inhibitory activity of themajor compound, EmiA, against drug-resistant pathogenic fungi was similar to that of amphotericin B (AmpB). At the same time, EmiA had no hemolytic activity towards human erythrocytes. In addition, EmiA demonstrated low cytotoxic activity towards the normal HPF line, but possessed cancer selectivity to the K-562 and HCT-116 cell lines. Emericillipsins from the alkalophilic fungus are promising treatment alternatives to licensed antifungal drugs for invasive mycosis therapy, especially for multidrug-resistant aspergillosis and cryptococcosis.
具有抗真菌和细胞毒性活性的新型抗菌肽源自嗜碱真菌VKPM F1428。我们之前报道过该菌株产生了具有强大抗真菌和细胞毒性特性的埃默里菌素A（EmiA）。对在特殊碱性培养基下获得的代谢产物进行进一步分析后，分离出了四种新的同源物（Emi B - E）。在这项工作中，我们报告了新合成的非核糖体抗菌肽埃默里菌素B - E的完整一级结构和详细的生物学活性。主要化合物EmiA对耐药致病真菌的抑制活性与两性霉素B（AmpB）相似。同时，EmiA对人红细胞没有溶血活性。此外，EmiA对正常HPF细胞系表现出低细胞毒性活性，但对K - 562和HCT - 116细胞系具有癌症选择性。来自嗜碱真菌的埃默里菌素有望成为治疗侵袭性真菌病的许可抗真菌药物的替代治疗选择，特别是对于多重耐药的曲霉病和隐球菌病。
